Research Paper Volume 12, Issue 21 pp 21355—21375

Association of folate intake and plasma folate level with the risk of breast cancer: a dose-response meta-analysis of observational studies

Xueting Ren1,2, *, , Peng Xu1,2, *, , Dai Zhang1,2, *, , Kang Liu3, , Dingli Song1,2, , Yi Zheng2, , Si Yang2, , Na Li1,2, , Qian Hao2, , Ying Wu2, , Zhen Zhai2, , Huafeng Kang2, &, , Zhijun Dai1,2, &, ,

  • 1 Department of Breast Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
  • 2 Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
  • 3 Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
* Equal contribution

Received: May 7, 2020       Accepted: July 25, 2020       Published: November 4, 2020
How to Cite

Copyright: © 2020 Ren et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Epidemiological studies showing the correlation between folate and the breast cancer risk have revealed inconsistent results. Hence, we conducted a dose-response meta-analysis of observational studies to obtain more reliable conclusions. We searched PubMed and Embase for studies published before April 2019 and identified 39 studies on folate intake and 12 studies on plasma folate level. The combined odds ratios (ORs) and 95% confidence intervals (CIs) were extracted to estimate the breast cancer risk. Folate intake was inversely correlated with the breast cancer risk when the highest and lowest categories (OR = 0.85, 95% CI = 0.79–0.92) were compared, and the dose-response result showed that folate intake had a linear correlation with the breast cancer risk. Moreover, a higher folate intake correlated with a lower breast cancer risk in premenopausal women (OR = 0.80, 95% CI = 0.66–0.97), but not in postmenopausal women (OR = 0.94, 95% CI = 0.83–1.06). However, plasma folate levels were not correlated with the breast cancer risk (OR = 0.98, 95% CI = 0.82–1.17). Folate intake was negatively correlated with the breast cancer risk; however, its practical clinical significance requires further study. Furthermore, additional folate supplements should be considered carefully.


OR: odds ratio; RR: relative risk; HR: hazard ratio; CI: confidence interval; BMI: body mass index; TNBC: triple negative breast cancer; DFE: dietary folate equivalent; AMORIS: Apolipoproteinrelated Mortality Risk; BRCA: Breast cancer; HRT: Hormone replacement therapy; MET: Metabolic Equivalent of Energy; OC: Oral contraceptives; EPIC: European Prospective Investigation into Cancer and Nutrition; SES: Socioeconomic status.